27 research outputs found

    Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

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    Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

    The Signal of Regard: William Godwin’s Correspondence Networks

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    © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. The letter is a gift of attention, in which the writer seeks to communicate regard by means of a signal crafted uniquely for the recipient. The concept of regard, as developed by the economic historian Avner Offer, indicates both attention and approbation. Adam Smith took it to be the driver of human exchange in emotions as much as in commerce. The exchange of regard captures the logic of a prodigious correspondent like William Godwin. The personalization of the gift signal is an attempt to convey an obligation to reciprocate. Godwin was attuned to this obligation and worked hard to fulfil it—with varying degrees of success. His correspondents encompassed almost every significant literary and political figure on the political left from the era of the French Revolution to the 1832 Reform Act. The children of the Godwin household were nourished by bonds of reciprocity, which they developed and extended when, in adulthood, they dispersed across Europe. The letters of Godwin and his correspondents embody a larger conversation, allowing intimacy to be preserved at a distance. The signals they once created for each other may now be received by us

    Time and Work in England, 1750–1830. By

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